Long-acting insulin analogues versus NPH insulin (human isophane insulin) for type 2 diabetes mellitus
Abstract
BACKGROUND: Despite indications from epidemiological trials that higher blood glucose concentrations are associated with a higher risk for developing micro- and macrovascular complications, evidence for a beneficial effect of antihyperglycaemic therapy in patients with type 2 diabetes mellitus is conflicting. Two large studies, the United Kingdom Prospective Diabetes Study (UKPDS) and the University Group Diabetes Program (UGDP), did not find a reduction of cardiovascular endpoints through improvement of metabolic control. The theoretical benefits of newer insulin analogues might result in fewer macrovascular and microvascular events. OBJECTIVES: To assess the effects of long-term treatment with long-acting insulin analogues (insulin glargine and insulin detemir) compared to NPH insulin in patients with type 2 diabetes mellitus. SEARCH STRATEGY: Studies were obtained from computerised searches of MEDLINE, EMBASE, The Cochrane Library and communication with experts in the field as well as insulin producing companies. SELECTION CRITERIA: Studies were included if they were randomised controlled trials in adults with diabetes mellitus type 2 and had a trial duration of at least 24 weeks. DATA COLLECTION AND ANALYSIS: Two authors independently assessed trial quality and extracted data. Pooling of studies by means of random-effects meta-analyses was performed. MAIN RESULTS: Six studies comparing insulin glargine to NPH (Neutral Protamine Hagedorn) insulin and two studies comparing insulin detemir to NPH insulin were identified. In these trials, 1715 patients were randomised to insulin glargine and 578 patients to insulin detemir. Duration of the included trials ranged from 24 to 52 weeks. Metabolic control, measured by glycosylated haemoglobin A1c (HbA1c) as a surrogate endpoint, and adverse effects did not differ in a clinical relevant way between treatment groups. While no statistically significant difference for severe hypoglycaemia rates was shown in any of the trials, the rate of symptomatic, overall and nocturnal hypoglycaemia was statistically significantly lower in patients treated with either insulin glargine or detemir. No evidence for a beneficial effect of long-acting analogues on patient-oriented outcomes like mortality, morbidity, quality of life or costs could be obtained. AUTHORS' CONCLUSIONS: Our analysis suggests, if at all only a minor clinical benefit of treatment with long-acting insulin analogues for patients with diabetes mellitus type 2 treated with "basal" insulin regarding symptomatic nocturnal hypoglycaemic events. Until long-term efficacy and safety data are available, we suggest a cautious approach to therapy with insulin glargine or detemir.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
The very rapid-acting and long-acting insulin analogues have not been shown to lower A1C levels more effectively than the older, rapid-acting or intermediate-acting formulations.
“The very rapid-acting and long-acting insulin analogues have not been shown to lower A1C levels more effectively than the older, rapid-acting or intermediate-acting formulations (71–73).”
From Medical Management of Hyperglycemia in Type 2 Diabetes: A Consensus Algorithm for the Initiation and Adjustment of Therapy (2009) · cites this paper as [71]
Cites
Measuring inconsistency in meta-analyses
Higgins, J. P. T., Thompson, S. G., Deeks, J. J., & Altman, D. G. (2003) · BMJ · doi:10.1136/bmj.327.7414.557 · Cited by 63,139 · see citing works
A Coefficient of Agreement for Nominal Scales
Cohen, J. (1960) · Educational and Psychological Measurement · doi:10.1177/001316446002000104 · Cited by 42,398 · see citing works
Quantifying heterogeneity in a meta‐analysis
Higgins, J. P. T., & Thompson, S. G. (2002) · Statistics in Medicine · doi:10.1002/sim.1186 · Cited by 36,763 · see citing works
Assessing the quality of reports of randomized clinical trials: Is blinding necessary?
Jadad, A. R., Moore, R. A., Carroll, D., Jenkinson, C., Reynolds, D. J. M., Gavaghan, D. J., & McQuay, H. J. (1996) · Controlled Clinical Trials · doi:10.1016/0197-2456(95)00134-4 · Cited by 17,582 · see citing works
Stratton, I. M. (2000) · BMJ · doi:10.1136/bmj.321.7258.405 · Cited by 9,059 · see citing works
Schulz (1995) · doi:10.1001/jama.1995.03520290060030 · Cited by 5,634 · see citing works
Ohkubo, Y., Kishikawa, H., Araki, E., Miyata, T., Isami, S., Motoyoshi, S., Kojima, Y., Furuyoshi, N., & Shichiri, M. (1995) · Diabetes Research and Clinical Practice · doi:10.1016/0168-8227(95)01064-k · Cited by 3,079 · see citing works
Turner, R. C., Millns, H., Neil, H. A. W., Stratton, I. M., Manley, S. E., Matthews, D. R., & Holman, R. R. (1998) · BMJ · doi:10.1136/bmj.316.7134.823 · Cited by 2,014 · see citing works
Riddle (2003) · doi:10.2337/diacare.26.11.3080 · Cited by 1,479 · see citing works
Hyperglycemie and Microvascular and Macrovascular Disease in Diabetes
Klein, R. (1995) · Diabetes Care · doi:10.2337/diacare.18.2.258 · Cited by 849 · see citing works
Lepore, M., Pampanelli, S., Fanelli, C., Porcellati, F., Bartocci, L., Di Vincenzo, A., Cordoni, C., Costa, E., Brunetti, P., & Bolli, G. B. (2000) · Diabetes · doi:10.2337/diabetes.49.12.2142 · Cited by 818 · see citing works
Kunz, R., & Oxman, A. D. (1998) · BMJ · doi:10.1136/bmj.317.7167.1185 · Cited by 770 · see citing works
Consensus Development Conference
Larsen, J. K., & Rogers, E. M. (1984) · Science Communication · doi:10.1177/107554708400500406 · Cited by 751 · see citing works
Kurtzhals, P., Schäffer, L., Sørensen, A., Kristensen, C., Jonassen, I., Schmid, C., & Trüb, T. (2000) · Diabetes · doi:10.2337/diabetes.49.6.999 · Cited by 739 · see citing works
Hermansen, K., Davies, M., Derezinski, T., Martinez Ravn, G., Clauson, P., Home, P., & on behalf of the Levemir Treat-to-Target Study Group (2006) · Diabetes Care · doi:10.2337/dc05-1365 · Cited by 627 · see citing works
Heise, T., Nosek, L., Rønn, B. B., Endahl, L., Heinemann, L., Kapitza, C., & Draeger, E. (2004) · Diabetes · doi:10.2337/diabetes.53.6.1614 · Cited by 614 · see citing works
Yki‐Järvinen, H., Dressler, A., Ziemen, M., & HOE 901/300s Study Group (2000) · Diabetes Care · doi:10.2337/diacare.23.8.1130 · Cited by 578 · see citing works
Basal Insulin Therapy in Type 2 Diabetes
Rosenstock, J., Schwartz, S. L., Clark, C. M., Park, G. D., Donley, D. W., & Edwards, M. B. (2001) · Diabetes Care · doi:10.2337/diacare.24.4.631 · Cited by 477 · see citing works
Heinemann, L., Linkeschova, R., Rave, K., Hompesch, B., Sedlak, M., & Heise, T. (2000) · Diabetes Care · doi:10.2337/diacare.23.5.644 · Cited by 474 · see citing works
King, G. L., Goodman, A. D., Buzney, S. M., Moses, A. C., & Kahn, C. R. (1985) · Journal of Clinical Investigation · doi:10.1172/jci111764 · Cited by 437 · see citing works
Insulin glargine or NPH combined with metformin in type 2 diabetes: The LANMET study
Yki-Järvinen, H., Kauppinen-Mäkelin, R., Tiikkainen, M., Vähätalo, M., Virtamo, H., Nikkilä, K., Tulokas, T., Hulme, S., Hardy, K., McNulty, S., et al. (2006) · Diabetologia · doi:10.1007/s00125-005-0132-0 · Cited by 434 · see citing works
The Mechanism of Protraction of Insulin Detemir, a Long-Acting, Acylated Analog of Human Insulin
Havelund, S., Plum, A., Ribel, U., Jonassen, I., Vølund, A., Markussen, J., & Kurtzhals, P. (2004) · Pharmaceutical Research · doi:10.1023/b:pham.0000036926.54824.37 · Cited by 431 · see citing works
Reduced Hypoglycemia Risk With Insulin Glargine
Rosenstock, J., DAILEY, G. E., Massi‐Benedetti, M., Fritsche, A., Lin, Z., & Salzman, A. (2005) · Diabetes Care · doi:10.2337/diacare.28.4.950 · Cited by 374 · see citing works
Adler, A., Boyko, E. J., Ahroni, J. H., Stensel, V. L., Forsberg, R. C., & Smith, D. G. (1997) · Diabetes Care · doi:10.2337/diacare.20.7.1162 · Cited by 363 · see citing works
Fritsche, A., Schweitzer, M. A., H�ring, H.-U., & and the 4001 Study Group* (2003) · Annals of Internal Medicine · doi:10.7326/0003-4819-138-12-200306170-00006 · Cited by 331 · see citing works
Haak, T., Tiengo, A., Draeger, E., Suntum, M., & Waldhäusl, W. K. (2004) · Diabetes Obesity and Metabolism · doi:10.1111/j.1463-1326.2004.00373.x · Cited by 277 · see citing works
Abraira, C. (1997) · Archives of Internal Medicine · doi:10.1001/archinte.157.2.181 · Cited by 253 · see citing works
Grant, M. B., Mames, R. N., Fitzgerald, C. R., Ellis, E. A., Aboufriekha, M., & Guy, J. (1993) · Diabetologia · doi:10.1007/bf00400229 · Cited by 190 · see citing works
Cardiovascular Events and Correlates in the Veterans Affairs Diabetes Feasibility Trial
Abraira, C. (1997) · Archives of Internal Medicine · doi:10.1001/archinte.1997.00440230053007 · Cited by 189 · see citing works
Mullins, P. R., Sharplin, P., Yki‐Järvinen, H., Riddle, M. C., & Häring, H. (2007) · Clinical Therapeutics · doi:10.1016/j.clinthera.2007.08.020 · Cited by 150 · see citing works
Benedetti, M. M., Humburg, E., Dressler, A., Ziemen, M., & for the 3002 Study Group (2003) · Hormone and Metabolic Research · doi:10.1055/s-2003-39080 · Cited by 149 · see citing works
Mühlhauser, I., Overmann, H., Bender, R., Bott, U., & Berger, M. (1998) · Diabetologia · doi:10.1007/s001250051065 · Cited by 117 · see citing works
Patient assessment of treatment satisfaction: methods and practical issues
Revicki, D. A. (2004) · Gut · doi:10.1136/gut.2003.034322 · Cited by 113 · see citing works
Therapy in Type 2 Diabetes: Insulin Glargine vs. NPH Insulin Both in Combination with Glimepiride
Eliaschewitz, F. G., Calvo, C., Valbuena, H., Ruiz, M., Aschner, P. J., Villena, J. E., Ramirez, L. A., & Jiménez, J. T. (2006) · Archives of Medical Research · doi:10.1016/j.arcmed.2005.10.015 · Cited by 109 · see citing works
Dunn, C. J., Plosker, G. L., Keating, G. M., McKeage, K., & Scott, L. J. (2003) · Drugs · doi:10.2165/00003495-200363160-00007 · Cited by 95 · see citing works
Chapman, T. M., & Perry, C. M. (2004) · Drugs · doi:10.2165/00003495-200464220-00008 · Cited by 91 · see citing works
Fonseca, V. A., Bell, D. S. H., Berger, S., Thomson, S. P., & Mecca, T. E. (2004) · The American Journal of the Medical Sciences · doi:10.1097/00000441-200411000-00007 · Cited by 60 · see citing works
Yokoyama, H., Tada, J., Kamikawa, F., Kanno, S., Yokota, Y., & Kuramitsu, M. (2006) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2005.12.009 · Cited by 51 · see citing works
Effects of Mixing Glargine and Short-Acting Insulin Analogs on Glucose Control
Kaplan, W., Rodríguez, L. M., Smith, O., Haymond, M. W., & Heptulla, R. A. (2004) · Diabetes Care · doi:10.2337/diacare.27.11.2739 · Cited by 41 · see citing works
Benefits of Combination Therapy of Insulin and Oral Hypoglycemic Agents
Garber, A. J. (2003) · Archives of Internal Medicine · doi:10.1001/archinte.163.15.1781 · Cited by 37 · see citing works
The Treat-to-Target Trial and Related Studies
Riddle, M. C. (2006) · Endocrine Practice · doi:10.4158/ep.12.s1.71 · Cited by 29 · see citing works
Long-term glycaemic control with insulin glargine in Type 2 diabetes
Kacerovsky-Bielesz, G., Dressler, A., & Freunscht, R. (2005) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2005.06.007 · Cited by 18 · see citing works
Gambert, S. R. (1987) · Springer eBooks · doi:10.1007/978-1-4899-1687-7_15 · Cited by 9 · see citing works
Initiating basal insulin therapy in patients with type 2 diabetes mellitus
STONEKING, K. B. (2005) · American Journal of Health-System Pharmacy · doi:10.1093/ajhp/62.5.510 · Cited by 6 · see citing works
Cada, D. J., Levien, T. L., & Baker, D. E. (2005) · Hospital Pharmacy · doi:10.1177/001857870504001208 · Cited by 2 · see citing works
[Lantus is superior in BOT (basic oral therapy) to standard mixed insulin].
(2004) · PubMed · Cited by 2 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009) · Diabetes Care · doi:10.2337/dc08-9025 · Cited by 3,834 · see citing works
Cryer, P. E., Axelrod, L., Grossman, A. B., Heller, S. R., Montori, V. M., Seaquist, E. R., & Service, F. J. (2009) · The Journal of Clinical Endocrinology & Metabolism · doi:10.1210/jc.2008-1410 · Cited by 1,277 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2021</i>
American Diabetes Association (2021) · Diabetes Care · doi:10.2337/dc21-s009 · Cited by 972 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2020</i>
American Diabetes Association (2020) · Diabetes Care · doi:10.2337/dc20-s009 · Cited by 914 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Care in Diabetes—2023</i>
ElSayed, N. A., Aleppo, G., Aroda, V. R., Bannuru, R. R., Brown, F. M., Bruemmer, D., Collins, B. S., Hilliard, M. E., Isaacs, D., Johnson, E. L., et al. (2023) · Diabetes Care · doi:10.2337/dc23-s009 · Cited by 851 · see citing works
9. Pharmacologic Approaches to Glycemic Treatment: <i>Standards of Medical Care in Diabetes—2019</i>
American Diabetes Association (2019) · Diabetes Care · doi:10.2337/dc19-s009 · Cited by 739 · see citing works
Nathan, D. M., Buse, J. B., Davidson, M. B., Ferrannini, E., Holman, R. R., Sherwin, R., & Zinman, B. (2009) · Diabetologia · doi:10.1007/s00125-008-1157-y · Cited by 712 · see citing works
Three-year efficacy of complex insulin regimens in type 2 diabetes
Holman, R. R., Farmer, A. J., Davies, M. J., Levy, J. C., Darbyshire, J. L., Keenan, J. F., & Paul, S. K. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0905479 · Cited by 667 · see citing works
Update on the treatment of type 2 diabetes mellitus
Marín-Peñalver, J. J., Martín-Timón, I., Sevillano-Collantes, C., & Cañizo-Gómez, F. J. D. (2016) · World Journal of Diabetes · doi:10.4239/wjd.v7.i17.354 · Cited by 647 · see citing works
Hemkens, L. G., Grouven, U., Bender, R., Günster, C., Gutschmidt, S., Selke, G. W., & Sawicki, P. T. (2009) · Diabetologia · doi:10.1007/s00125-009-1418-4 · Cited by 607 · see citing works
Glucocorticoid-induced hyperglycemia
Clore, J. N., & Thurby-Hay, L. (2009) · Endocrine Practice · doi:10.4158/ep08331.rar · Cited by 508 · see citing works
Ratner, R. E., Gough, S. C. L., Mathieu, C., Del Prato, S., Bode, B., Mersebach, H., Endahl, L., & Zinman, B. (2013) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12032 · Cited by 346 · see citing works
Khunti, K., Alsifri, S., Aronson, R., Cigrovski Berković, M., Enters‐Weijnen, C., Forsén, T., Galstyan, G., Geelhoed‐Duijvestijn, P., Goldfracht, M., Gydesen, H., et al. (2016) · Diabetes Obesity and Metabolism · doi:10.1111/dom.12689 · Cited by 276 · see citing works
Long-acting insulin analogues versus NPH human insulin in type 2 diabetes
Monami, M., Marchionni, N., & Mannucci, E. (2008) · Diabetes Research and Clinical Practice · doi:10.1016/j.diabres.2008.04.007 · Cited by 211 · see citing works
Insulin therapy for type 2 diabetes.
Swinnen, S. G., Hoekstra, J. B., & DeVries, J. H. (2009) · Diabetes Care · doi:10.2337/dc09-s318 · Cited by 181 · see citing works
Pharmacologic Glycemic Management of Type 2 Diabetes in Adults: 2020 Update
Lipscombe, L., Butalia, S., Dasgupta, K., Eurich, D. T., MacCallum, L., Shah, B. R., Simpson, S., & Senior, P. A. (2020) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2020.08.001 · Cited by 153 · see citing works
Rys, P., Wojciechowski, P., Rogoz-Sitek, A., Niesyczyński, G., Lis, J., Syta, A., & Malecki, M. T. (2015) · Acta Diabetologica · doi:10.1007/s00592-014-0698-4 · Cited by 101 · see citing works
Why is there no generic insulin? Historical origins of a modern problem
Greene, J. A., & Riggs, K. R. (2015) · New England Journal of Medicine · doi:10.1056/nejmms1411398 · Cited by 81 · see citing works
Lipska, K. J., Parker, M. M., Moffet, H. H., Huang, E. S., & Karter, A. J. (2018) · JAMA · doi:10.1001/jama.2018.7993 · Cited by 76 · see citing works
Heller, S., White, D., Lee, E., Lawton, J., Pollard, D., Waugh, N., Amiel, S., Barnard, K., Beckwith, A., Brennan, A., et al. (2017) · Health Technology Assessment · doi:10.3310/hta21200 · Cited by 73 · see citing works
Zhang, X.-W., Zhang, X.-L., Xu, B., & Kang, L.-N. (2018) · Acta Diabetologica · doi:10.1007/s00592-018-1107-1 · Cited by 44 · see citing works
Mannucci, E., Caiulo, C., Naletto, L., Madama, G., & Monami, M. (2021) · Endocrine · doi:10.1007/s12020-021-02889-6 · Cited by 30 · see citing works
Comparative effectiveness and safety of different basal insulins in a real-world setting
Ji, L., Zhang, P., Zhu, D., Lu, J., Guo, X., Wu, Y., Li, X., Ji, J., Jia, W., Yang, W., et al. (2017) · Diabetes, Obesity and Metabolism · doi:10.1111/dom.12920 · Cited by 13 · see citing works
Lega, I. C., Yale, J.-F., Chadha, A., Paty, B., Roscoe, R., Snider, M., Steier, J., Bajaj, H. S., Barnes, T., Gilbert, J., et al. (2023) · Canadian Journal of Diabetes · doi:10.1016/j.jcjd.2023.08.003 · Cited by 12 · see citing works
Glucose-Lowering Medication Use in CKD: Analysis of US Medicare Beneficiaries Between 2007 and 2016
Zhao, J. Z., Weinhandl, E. D., Carlson, A. M., & St. Peter, W. L. (2021) · Kidney Medicine · doi:10.1016/j.xkme.2020.09.016 · Cited by 9 · see citing works
- Authors
- Horvath, K., Jeitler, K., Berghold, A., Ebrahim, S. H., Gratzer, T. W., Plank, J., Kaiser, T., Pieber, T. R., & Siebenhofer, A.
- Affiliations
- Medical University of Graz (AT)
- Institute for Quality and Efficiency in Health Care (DE)
- Venue
- Cochrane Database of Systematic Reviews
- Publisher
- Wiley
- Published
- 2007-04-18
- Issue
- 2
- Pages
- CD005613-CD005613
- ISSN
- 1361-6137 (ISSN-L)
- 1465-1858
- OpenAlex
- W1953393606
- Cited by
- 366
- References
- 47
- Citations by year
- 2026: 3 · 2025: 4 · 2024: 2 · 2023: 10 · 2022: 13 · 2021: 16 · 2020: 23 · 2019: 19 · 2018: 30 · 2017: 25 · 2016: 26 · 2015: 22 · 2014: 23 · 2013: 23 · 2012: 25
- FWCI
- 3.83
- Type
- journal article
- Language
- en
- Update notices
- new_version (2020-11-09)
- Open access
- closed
- Locations
- Cochrane Database of Systematic Reviews (publishedVersion)
- PubMed (publishedVersion)
- LSHTM Research Online (London School of Hygiene and Tropical Medicine) (acceptedVersion)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Treatment and Management
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes Management and Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- type 2 diabetes, long-acting insulin analogues, insulin glargine, insulin detemir, NPH insulin, basal insulin, glycemic control, HbA1c, hypoglycemia, nocturnal hypoglycemia, adverse effects, cardiovascular outcomes, microvascular complications, cost-effectiveness, quality of life, mortality, morbidity
- MeSH terms
- Insulin Glargine, Insulin Detemir, Diabetes Mellitus, Type 2, Humans, Hypoglycemic Agents, Insulin, Insulin, Isophane, Randomized Controlled Trials as Topic, Insulin, Long-Acting
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
